Project Summary The requested instrumentation in this proposal is a high resolution mass spectrometer coupled to an ultra high performance liquid chromatograph (UHPLC) system that will be used for untargeted metabolomics and lipidomics experiments. Specifically, we are requesting funds for a ThermoFisher Scientific Q Exactive Plus with Vanquish UHPLC. This instrument will be housed in the University of Pittsburgh Biomedical Mass Spectrometry Center (BioMS Center). The BioMS Center is a campus-wide shared facility dedicated to advancing the use and application of mass spectrometry in basic, clinical, and translational science. The BioMS Center is supported by the University of Pittsburgh Schools of the Health Sciences and the University of Pittsburgh Cancer Institute. Dr. Nathan A. Yates is the Scientific Director and Drs. Xuemei Zeng and Stacy L. Wendell are Directors of Proteomics and Metabolomics, respectively. Until last 2015 the BioMS Center only supported proteomic projects. In 2015, Dr. Yates was awarded an S10 for a triple stage quadrupole mass spectrometer that is being used for targeted small molecule analysis. The BioMS Center would like to expand its capabilities to also provide untargeted metabolomics, thus we are requesting a high resolution instrument. This proposal highlights the need of untargeted metabolomics and lipidomics capabilities from 22 users (19 with NIH funding) from multiple NIH institutes or centers. Additionally the metabolomics core of the BioMS Center has established ongoing collaborations with institutes and centers at Pitt including the Center for Metabolism and Mitochondrial Medicine, the Center for Medicine and the Microbiome and the Institute of Aging. Projects range from various cancer studies to B and T cell differentiation and to clinical studies focused on asthma, sepsis and pulmonary hypertension. Expertise in the BioMS Center includes staff that is responsible for instrument maintenance, sample preparation, method development and data analysis, including large data sets that require the use of bioinformatics software for differential mass spectrometry experiments. Dr. Wendell has extensive expertise in liquid chromatography-mass spectrometry small molecule method development and sample preparation. Dr. Deshpande joined the BioMS Center in early 2016 as a staff scientist who is working with Dr. Wendell and responsible for the day to day upkeep and sample analysis. His expertise is in mass spectrometry and flux analysis. If awarded, this grant will fill an unmet need at the University of Pittsburgh and accelerate research activity leading to more publications and grant submissions.